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Fig. 6 | Acta Neuropathologica Communications

Fig. 6

From: Inhibition of acid sphingomyelinase reduces reactive astrocyte secretion of mitotoxic extracellular vesicles and improves Alzheimer’s disease pathology in the 5xFAD mouse

Fig. 6

Imipramine reduces ceramide, GFAP, and Aβ levels in 5XFAD brain-derived EVs. A NTA measurement of EVs isolated from forebrain normalized to protein content of starting tissue. Bar graph represents average ± SD with each N = 4/group. B Representative particle counts on different CD9 capture spots. Counts of GFAP (GFAP+) and Cer (Cer+) positive EVs, CD9 captured. Bar graph represents average ± SD. for three capture spots of N = 4 (pooled)/group. C Representative images and pie chart showing percentage of colocalization of GFAP+ with Cer+ in CD9 captured EVs of 5xFAD vehicle and Imipramine treated groups. D Quantification of C14:0, C16:0, C18:0, C18:1, C20, C20:1, C22:0, C24:0, C24:1 Cer by mass spectrometry of brain EVs. Bar graph represents average ± SD with each N = 3/group. E1-42 quantification in brain derived EVs by ELISA. Bar graph represents average ± SD with each N = 4/group. F Neuronal toxicity determined by LDH release after 18 h incubation with brain derived EVs. Box and Whiskers plot with each N = 4/group. One-way ANOVA followed by Tukey postdoc (*p < 0.05, **p < 0.01, ***p < 0.0001, ****p < 0.0001)

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